Cancer Genet. 2018 Oct 10. pii: S2210-7762(18)30060-7. doi: 10.1016/j.cancergen.2018.07.003. [Epub ahead of print]
Assessing copy number aberrations and copy neutral loss of heterozygosity across the genomeas best practice: An evidence based review of clinical utility from the cancer genomicsconsortium (CGC) working group for myelodysplastic syndrome, myelodysplastic/myeloproliferative and myeloproliferative neoplasms.
Kanagal-Shamanna R1, Hodge JC2, Tucker T3, Shetty S4, Yenamandra A5, Dixon-McIver A6, Bryke C7, Huxley E8, Lennon PA9, Raca G10, Xu X11, Jeffries S8, Quintero-Rivera F12, Greipp PT13, Slovak ML14, Iqbal MA15, Fang M16.
Multiple studies have demonstrated the utility of chromosomal microarray (CMA) testing to identify clinically significant copy number alterations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) in myeloid malignancies. However, guidelines for integrating CMA as a standard practice for diagnostic evaluation, assessment of prognosis and predicting treatment response are still lacking. CMA has not been recommended for clinical work-up of myeloid malignancies by the WHO 2016 or the NCCN 2017 guidelines but is a suggested test by the European LeukaemiaNet 2013 for the diagnosis of primary myelodysplastic syndrome (MDS). The Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms systematically reviewed peer-reviewed literature to determine the power of CMA in (1) improving diagnostic yield, (2) refining risk stratification, and (3) providing additional genomic information to guide therapy. In this manuscript, we summarize the evidence base for the clinical utility of array testing in the workup of MDS, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and myeloproliferative neoplasms (MPN). This review provides a list of recurrent CNAs and CN-LOH noted in this disease spectrum and describes the clinical significance of the aberrations and how they complement gene mutation findings by sequencing. Furthermore, for new or suspected diagnosis of MDS or MPN, we present suggestions for integrating genomic testing methods (CMA and mutation testing by next generation sequencing) into the current standard-of-care clinical laboratory testing (karyotype, FISH, morphology, and flow).
Copy neutral loss of heterozygosity; Copy number aberrations; Microarray; Myelodysplastic syndrome; Myeloproliferative neoplasm; Next-generation sequencing